Discovery offers new hope to repair spinal cord injuries

Scientists produce a type of stem cell-derived neuron that could potentially help restore movement

Date:April 24, 2017Source:Gladstone InstitutesSummary:Scientists have created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. These cells, called V2a interneurons, transmit signals in the spinal cord to help control movement. When the researchers transplanted the cells into mouse spinal cords, the interneurons sprouted and integrated with existing cells.Share:

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Todd McDevitt (right), Jessica Butts (center) and Dylan McCreedy (left) created a special type of neuron from human stem cells that could potentially repair spinal cord injuries.Credit: Chris Goodfellow, Gladstone Institutes

Scientists at the Gladstone Institutes created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. These cells, called V2a interneurons, transmit signals in the spinal cord to help control movement. When the researchers transplanted the cells into mouse spinal cords, the interneurons sprouted and integrated with existing cells.
V2a interneurons relay signals from the brain to the spinal cord, where they ultimately connect with motor neurons that project out to the arms and legs. The interneurons cover long distances, projecting up and down the spinal cord to initiate and coordinate muscle movement, as well as breathing. Damage to V2a interneurons can sever connections between the brain and the limbs, which contributes to paralysis following spinal cord injuries.
"Interneurons can reroute after spinal cord injuries, which makes them a promising therapeutic target," said senior author Todd McDevitt, PhD, a senior investigator at Gladstone. "Our goal is to rewire the impaired circuitry by replacing damaged interneurons to create new pathways for signal transmission around the site of the injury."
Several clinical trials are testing cell replacement therapies to treat spinal cord injuries. Most of these trials involve stem cell-derived neural progenitor cells, which can turn into several different types of brain or spinal cord cells, or oligodendrocyte progenitor cells, which create the myelin sheaths that insulate and protect nerve cells. However, these approaches either do not attempt or cannot reliably produce the specific types of adult spinal cord neurons, such as V2a interneurons, that project long distances and rebuild the spinal cord.
In the current study, published in the Proceedings of the National Academy of Sciences, the researchers produced V2a interneurons from human stem cells for the first time. They identified a cocktail of chemicals that gradually coaxed the stem cells to develop from spinal cord progenitor cells to the desired V2a interneurons. By adjusting the amounts of three of the chemicals and when each one was added, the scientists refined their recipe to create large amounts of V2a interneurons from stem cells.
"Our main challenge was to find the right timing and concentration of the signaling molecules that would yield V2a interneurons instead of other neuronal cell types, such as motor neurons," said first author Jessica Butts, a graduate student in the McDevitt lab. "We used our knowledge of how the spinal cord develops to identify the right combination of chemicals and to improve our procedure to give us the highest concentration of V2a interneurons."
Working in collaboration with Linda Noble, PhD, at the University of California, San Francisco (UCSF), the scientists transplanted the V2a interneurons into the spinal cords of healthy mice. In their new environment, the cells matured appropriately and integrated with existing spinal cord cells. Importantly, the mice moved normally after the interneurons were transplanted and showed no signs of impairment.
"We were very encouraged to see that the transplanted cells sprouted long distances in both directions -- a key characteristic of V2a interneurons -- and that they started to connect with the relevant host neurons," said co-author Dylan McCreedy, PhD, a postdoctoral scholar at Gladstone.
The researchers say their next step is to transplant the cells into mice with spinal cord injuries to see if the V2a interneurons can help to restore movement after damage has occurred. They are also interested in exploring the potential role of these cells in models of neurodegenerative movement disorders such as amyloid lateral sclerosis.

]]>Curemj23http://sci.rutgers.edu/forum/showthread.php?260945-Discovery-offers-new-hope-to-repair-spinal-cord-injuriesPossible opportunityhttp://sci.rutgers.edu/forum/showthread.php?260873-Possible-opportunity&goto=newpost
Sat, 09 Sep 2017 19:17:12 GMTSo it seems I may have an opportunity to receive stem cell treatment in S. Korea at Dr. Kims Stem cell Clinic (http://www.kmhglobal.com/department/dr-kims-stem-cell-clinic) for my c4-c5 paralysis. Before I make a decision there are still more questions that need to be answered. I was curious if...So it seems I may have an opportunity to receive stem cell treatment in S. Korea at Dr. Kims Stem cell Clinic (http://www.kmhglobal.com/department/...em-cell-clinic) for my c4-c5 paralysis. Before I make a decision there are still more questions that need to be answered. I was curious if anyone has heard of this clinic and if they could offer any professional insight. We are having a phone conference meeting this Friday to get a little more information and clarity.

Supposedly the Korean government will decide whether they will cover the cost of my flight and treatment at the end of this month as part of a documentary they are filming as a public relation with the US. I'm unsure of what to do but I think I'd be foolish not to, at the very least, listen to what they are talking about.
]]>Curejaemchttp://sci.rutgers.edu/forum/showthread.php?260873-Possible-opportunityNerve growthhttp://sci.rutgers.edu/forum/showthread.php?260833-Nerve-growth&goto=newpost
Fri, 01 Sep 2017 22:36:11 GMTI am still getting more returns after 12 years. It was stagnant for a long time but I am getting big changes and am a little hopeful the pain will diminish.I am still getting more returns after 12 years. It was stagnant for a long time but I am getting big changes and am a little hopeful the pain will diminish.
]]>Curestevegalliazzohttp://sci.rutgers.edu/forum/showthread.php?260833-Nerve-growthStem Cell Clinic raided by US Marshallshttp://sci.rutgers.edu/forum/showthread.php?260815-Stem-Cell-Clinic-raided-by-US-Marshalls&goto=newpost
Tue, 29 Aug 2017 23:54:36 GMT** Smallpox vaccine used in risky cancer therapy seized from San Diego stem cell company
San Diego U-T
August 29, 2017
by Bradley J. Fikes **
Cancer patients were given an unapproved and potentially dangerous treatment from a San Diego stem cell company that contained smallpox vaccine, the...

(KLD)
]]>CureSCI-Nursehttp://sci.rutgers.edu/forum/showthread.php?260815-Stem-Cell-Clinic-raided-by-US-MarshallsMiami Projects trialhttp://sci.rutgers.edu/forum/showthread.php?260812-Miami-Projects-trial&goto=newpost
Tue, 29 Aug 2017 17:55:37 GMTHas anyone herd anymore about their trials and how the patients progressed? Did anyone here do it?
https://medicalxpress.com/news/2017-03-university-miami-successfully-sci-clinical.htmlHas anyone herd anymore about their trials and how the patients progressed? Did anyone here do it?

https://medicalxpress.com/news/2017-...-clinical.html
]]>Cure#LHB#http://sci.rutgers.edu/forum/showthread.php?260812-Miami-Projects-trialSUMMARY: DR. REGGIE EDGERTON, The Spinal Cord Injury Project Summer Open Househttp://sci.rutgers.edu/forum/showthread.php?260809-SUMMARY-DR-REGGIE-EDGERTON-The-Spinal-Cord-Injury-Project-Summer-Open-House&goto=newpost
Mon, 28 Aug 2017 15:05:09 GMT*SUMMARY: DR. REGGIE EDGERTON
The Spinal Cord Injury Project
Summer Open House
Thursday, 20 July 2017 *
This is a synopsis of Dr. Edgerton?s presentation to the W. M. Keck Center Summer Open House. Additional details on his research are available on his website. With appreciation to the...SUMMARY: DR. REGGIE EDGERTON
The Spinal Cord Injury Project
Summer Open House
Thursday, 20 July 2017

This is a synopsis of Dr. Edgerton?s presentation to the W. M. Keck Center Summer Open House. Additional details on his research are available on his website. With appreciation to the students who took notes during Dr. Edgerton?s presentation at the Summer Open House.

At the invitation of the W. M. Keck Center for Collaborative Neuroscience and the Spinal Cord Injury Project, Dr. Reggie Edgerton gave two presentations at Rutgers University. The first was a scientific presentation for faculty and students co-sponsored by the Department of Cell Biology and Neuroscience entitled: Mechanisms of spinal neuromodulation and plasticity post paralysis.
Dr. Edgerton?s second talk: Spinal Cord Stimulation: What We?ve Learned ? What?s Next! was given to the Summer Open House hosted by the W. M. Keck Center for Collaborative Neuroscience.

Dr. Edgerton began this talk by saying he was going to present facts and it was up to each person in the audience to make their own decision about hope. He then stated that ?we are going to have to reassess our thinking about how the spinal cord works, and how the brain interactively works with the spinal cord. The brain has to learn to work with the spinal cord because they both have new circuitry.?

There are several potential approaches being studied:
Agonists
Pharmacology
indwelling electrodes
epidural electrodes (on top of the dura)
transcutaneous electrodes.

All use common mechanisms, show potential, and are in their infancy.

Regardless of the type, neuromodulation is different from FES: in FES the device is turned on and movement results; in neuromodulation, when the device is turned on, the person decides whether to move or not.
He discussed his research on neuromodulation:

● Using neuromodulation to regain some of lost function potentially could improve functions such as, but not limited to, sensory, sexual, temperature control, etc. This potentially also could lower health cost.

● The theory behind his work is that after injury the neural circuit baseline potential drops below the effective threshold, hence, no movement occurs. Through neuromodulation, the baseline potential can be artificially raised so that it reaches the motor threshold.

● Neuromodulation was done on five patients, and they were trained for 18 weeks:
Prior to training, the patients only can move a little (voluntary oscillation) but with stimulation there is a significant increase in movement. After 18 weeks of training, the patients exhibited notable signs of improvement, as they could now move their legs in a visible kicking/walking motion unaided.

● Another experiment also was done, in which patients were trained to move their hands. After further training, they gained greater strength in their hands.

● The process builds on the amazing redundancy in the spinal cord and involves training, learning, and retention.
This provides evidence that residual function post-injury can be enhanced by training, which over time can lead to the regaining of voluntary and autonomic function.
Voluntary movement from residual function post-injury can be improved through training.

● The spinal cord can ?learn?. A study was done on rats, where their paw trajectories were observed walking on a treadmill.

● Untrained rats had unsteady and unpredictable trajectories, while trained rats were able to keep significantly more stable trajectories (similar to a ballistic arc).

QUESTIONS

When you did double injury instantaneously, why was recovery much less as compared to recovery gained after doing the injury one after the other?

If you cut two sections of the injury area at the same time, you do not allow for regeneration or reorganization of the tissue. On the contrary, if you cut two injured sections one after the other, the first section will start regeneration of tissue. This is the reason for better recovery when doing the injuries one after the other.

Which device is better in helping with the movement after injury?

Transcutaneous stimulation probably is more effective than epidural stimulation because, as the experiment results show, more of the injured patients stand. As a side note, they are yet to do testing stimulations to observe and analyze the patients? will to move their legs even before they move them.

While bringing the RMP (Resting Membrane Potential) of neurons back to normal, did you see any other positive or negative side effects?

Yes, in general there are both acute effects on the autonomous nervous system (ANS) and chronic effects on blood pressure, bladder, etc. These two effects are relatively common responses. It also appears that specific parts of the spinal cord can be modulated and stimulated. So we need to use the stimulation model carefully to achieve results.

What are some of the barriers that you have come across in combining therapies?

The most important barrier is in how much neuromodulation can be obtained and gauged. The first thing that happens in your body is not movement, but preparation of the brain for carrying out movement.

For the diagram of the circuit, if you hamper a part or whole of the circuit, does the brain adjust to compensate?

The exact mechanism is unknown because the order of information flow has not yet been determined. Nevertheless, the brain and spinal cord neurons function repeatedly in a certain way. Hence, a specific pattern gets reinforced and spinal cord learning occurs.

Did you notice if muscle atrophy and joint dissociation effect the ability to stand?

I first came here to see what Dr Wise Young had to say about cord blood banking. I read his post in 2009 about his evolving attitude on cord blood banking and read some of Jim's reposts of Dr Young's previous statements in 2015.

Apparently StemCyte works with researchers to supply cells for their studies (in-part to promote the quality of their storage methods thereby providing the viability of the cells). They supply the cells for Wise's trials and over the course of that work he became their Global Medical Director among his other duties (very cool).

You can see him all over youtube when you search stemcyte.
This video is a very good overview of Dr. Wise's experience with StemCyte from 2013: https://www.youtube.com/watch?v=AaD5oVoBt7c
You can hear his skepticism on tissue (as opposed to blood) banking (until there is settled science on the efficacy) at the end of this video

So in spending the afternoon researching cord blood banking and the different companies that offer private banking I came across theses notable standout options. I'm mostly looking at total price vs quality for banking cord blood with ~20 years of storage.

StemCyte https://stemcyte.com/
Pros: Dr Wise Young approved, more successful transplants (uses) than any other company
Cons: Not the most affordable (~$4k), unclear if it is stored in speratable storage (to avoid making the choice between child's potential use and the future use for SCI).

Americord https://www.americordblood.com/
Pros: Straightforward good pricing for banking + storage (~$3k), seems to be trying to create a competitive high quality product
Cons:heavily advertised, newer company, limited actual transplants, unclear if it is stored in speratable storage (to avoid making the choice between child's potential use and the future use for SCI)

Alphacord https://www.alphacord.com/
Pros: least expensive ($2k), newer company, say they are 100% successful in transplants
Cons: apparently only four transplants, unclear if it is stored in speratable storage (to avoid making the choice between child's potential use and the future use for SCI), doesn't ship cord blood temperature controlled (supposedly it's fine for 48hrs at room temp)

It should be said that your child's UCB isn't very likely to be a good match for a parent (but could be).

At this point I will try after the weekend to call CryoCell to test their price matching. if they can match the Americord $3k price (which seems doubtful), I will probably go that route. Unless...

Is Dr. Wise Young in a position with StemCyte to be able to offer a special discount to his SCI population (with the possibility of donation to science/research if unused)?

After I call CryoCell I might check with StemCyte to see if they already have an SCI discount on the record (perhaps someone has already been down this path before)?

Otherwise, I'll probably pick between the cheaper two options (AlphaCord/Americord) or simply not doing it at all. As the whole idea of the cells being useful to myself or someone in my family (like my soon-to-be daughter) is admittedly a long shot and there is likely to be a better use for that money (like additional donation to cure research or college fund).

I'll keep the thread updated -- thanks for reading!
Anthony
]]>Curemaglitohttp://sci.rutgers.edu/forum/showthread.php?260799-DrWiseYoung-StemCyte-Medical-Director-possible-discount-for-SCI-population-UCB-bankNerve fibers regenerated with molecular mixhttp://sci.rutgers.edu/forum/showthread.php?260772-Nerve-fibers-regenerated-with-molecular-mix&goto=newpost
Tue, 22 Aug 2017 18:47:08 GMThttp://www.medicalnewstoday.com/articles/319011.phphttp://www.medicalnewstoday.com/articles/319011.php
]]>CureKIMhttp://sci.rutgers.edu/forum/showthread.php?260772-Nerve-fibers-regenerated-with-molecular-mixWhere do we stand? No pun intendedhttp://sci.rutgers.edu/forum/showthread.php?260767-Where-do-we-stand-No-pun-intended&goto=newpost
Tue, 22 Aug 2017 02:14:11 GMTI might come look at this webpage once every six months, and it still is the same thing. I figured I would hear on the news if there was a repair for spinal cord injuries. I guess were in the same situation that we were 20 years ago when I first got injured C3? I was in one of the well-known rehabs...I might come look at this webpage once every six months, and it still is the same thing. I figured I would hear on the news if there was a repair for spinal cord injuries. I guess were in the same situation that we were 20 years ago when I first got injured C3? I was in one of the well-known rehabs in West Orange New Jersey inpatient and they could not believe that shape I am in after 20 years. Now can someone tell me in simple words where we are on a repair for this injury? Anybody have any predictions on time? I still live my life at 50 years old but I'm getting ready to say screw it. I live long enough like this. Just want to hear what's new. Any help would be greatly appreciated.
]]>CureKeithhttp://sci.rutgers.edu/forum/showthread.php?260767-Where-do-we-stand-No-pun-intendedAre we owed a cure by those saving us?http://sci.rutgers.edu/forum/showthread.php?260753-Are-we-owed-a-cure-by-those-saving-us&goto=newpost
Sat, 19 Aug 2017 19:25:08 GMTAre we owed a cure by those saving us?
Can it be ? Should it be?
Ever consider this?
Great, the surgeons get kudos for saving us. They hone their skills, try different surgeries to re-connect our vertebrae.
Then their colleagues get them benefit of studying us for however long we live.
Test...Are we owed a cure by those saving us?
Can it be ? Should it be?
Ever consider this?

Great, the surgeons get kudos for saving us. They hone their skills, try different surgeries to re-connect our vertebrae.
Then their colleagues get them benefit of studying us for however long we live.
Test wheelchairs and gadgets on us. Keep an industry in practice, earn$
We enter clinical trials for care technologies. Pharma wins big on us.
Some of us with $ can survive, some have meaningful lives, still, others have menial lives, while the rest of us fade away, families destroyed.
To what end?
"Cure, cure, cure is coming" is whispered in our ears.
"Hang in, be patient" "Enjoy today, albeit you're a specimen slide"
"Ok, yeah pain is tough, neuro and related sci issues suck"
"But each day is one day closer to getting your body back"
> Enough of this, maybe?
You guys studied us enough, time to get your shit together and fix us: or admit you can't.
We're not fodder for your studies, poster children for $ revenue.
Next time it could be your accident.
Remember The March of Dimes, there's enough $ out there that most of a cure could be accomplished in a few short years; if it was taken seriously like Polio.
Is this asking too much?
Or should rehabs stop painting rosy pictures to the hi, hard to care for quads, and give us a choice and means to do it?
]]>CureTim C.http://sci.rutgers.edu/forum/showthread.php?260753-Are-we-owed-a-cure-by-those-saving-usStem Cell Researchhttp://sci.rutgers.edu/forum/showthread.php?260749-Stem-Cell-Research&goto=newpost
Fri, 18 Aug 2017 16:31:31 GMTOut of curiosity, what are the adverse effects of stem cells for SCI? Also has there been any studies showing improvements in stem cells for SCI patients?Out of curiosity, what are the adverse effects of stem cells for SCI? Also has there been any studies showing improvements in stem cells for SCI patients?
]]>Curejaemchttp://sci.rutgers.edu/forum/showthread.php?260749-Stem-Cell-ResearchNew surgical technique (video)http://sci.rutgers.edu/forum/showthread.php?260703-New-surgical-technique-(video)&goto=newpost
Sat, 12 Aug 2017 21:57:05 GMTI think another video about this was posted a few days ago but I forget if it was this same one or a similar one. I am not sure that I really fully understand this so can some members please discuss
...I think another video about this was posted a few days ago but I forget if it was this same one or a similar one. I am not sure that I really fully understand this so can some members please discuss